Determinants of lung function across childhood in the Severe Asthma Research Program (SARP) 3

Abstract

Background: Children with asthma are at risk for low lung function extending into adulthood, but understanding of clinical predictors is incomplete.

Objective: We sought to determine phenotypic factors associated with FEV₁ throughout childhood in the Severe Asthma Research Program 3 pediatric cohort.

Methods: Lung function was measured at baseline and annually. Multivariate linear mixed-effects models were constructed to assess the effect of baseline and time-varying predictors of prebronchodilator FEV₁ at each assessment for up to 6 years. All models were adjusted for age, predicted FEV₁ by Global Lung Function Initiative reference equations, race, sex, and height. Secondary outcomes included postbronchodilator FEV₁ and prebronchodilator FEV₁/forced vital capacity.

Results: A total of 862 spirometry assessments were performed for 188 participants. Factors associated with FEV₁ include baseline Feno (B, -49 mL/log₂ PPB; 95% CI, -92 to -6), response to a characterizing dose of triamcinolone acetonide (B, -8.4 mL/1% change FEV₁ posttriamcinolone; 95% CI, -12.3 to -4.5), and maximal bronchodilator reversibility (B, -27 mL/1% change postbronchodilator FEV₁; 95% CI, -37 to -16). Annually assessed time-varying factors of age, obesity, and exacerbation frequency predicted FEV₁ over time. Notably, there was a significant age and sex interaction. Among girls, there was no exacerbation effect. For boys, however, moderate (1-2) exacerbation frequency in the previous 12 months was associated with -20 mL (95% CI, -39 to -2) FEV₁ at each successive year. High exacerbation frequency (≥3) 12 to 24 months before assessment was associated with -34 mL (95% CI, -61 to -7) FEV₁ at each successive year.

Conclusions: In children with severe and nonsevere asthma, several clinically relevant factors predict FEV₁ over time. Boys with recurrent exacerbations are at high risk of lower FEV₁ through childhood.

Keywords: Severe asthma; asthma exacerbations; lung function; spirometry.